The diversity of neurons that populate the mature central nervous system (CNS) develop through a highly similar series of regulatory cell fate decisions that lead to the individual specification of neuronal fates in both vertebrates and invertebrates. Proper neuronal fate specification underlies the creation of the intricate neuronal network that comprises the mature CNS of both vertebrates and invertebrates. Our research focuses on the earliest steps of neural development through to the individual fate specification of neurons in the Drosophila CNS. We identified more than 50 genes required for the development of a specific subset of Drosophila CNS neurons via mutagenic screens. We currently focus on several of these genes which act during distinct steps of neural development to restrict progressively the developmental potential of cells as they acquire individual neuronal fates. The goals of this proposal are to understand the genetic and molecular basis of neural determination in the Drosophila CNS. Specifically, we propose: (1) to understand how CNS cell fates are specified along the dorsoventral axis of the neuroectoderm; (2) to identify new genes that regulate asymmetric neural progenitor divisions via genetic modifier screens; (3) to determine the molecular nature of sanpodo (see below) and elucidate the molecular mechanism through which sanpodo enables sibling cells to acquire distinct fates; and, (4) to understand the role of extra-extra, the Drosophila homolog of the vertebrate motor neuron promoting genes FIB9 and MNR2, during CNS development. Remarkable parallels exist between Drosophila and vertebrate CNS development, these parallels begin with the formation and patterning of the Drosophila neuroectoderm and vertebrate neural plate and continue unabated through the individual specification of Drosophila and vertebrate neurons. Thus, the identification, isolation and characterization of genes that control neuronal fate specification in Drosophila should continue to yield fundamental insights into the molecular mechanisms that regulate cell fate determination and cell differentiation in mammalian nervous systems.